tbuckley/cabot-search huggingface dataset:
Fasudil alleviates the vascular endothelial dysfunction and several phenotypes of Fabry disease
Authors: Jong Bin Choi, Dong-Won Seol, Hyo-Sang Do, Hee-Young Yang, Taek-Min Kim, Youkyeong Gloria Byun, Jae-Min Park, Jinhyuk Choi, Seon Pyo Hong, Won-Suk Chung, Jae Myoung Suh, Gou Young Koh, Beom Hee Lee, Gabbine Wee, Yong-Mahn Han
Journal: Molecular Therapy (2023)

Fabry disease (FD), a lysosomal storage disorder, is caused by defective α-galactosidase (GLA) activity, which results in the accumulation of globotriaosylceramide (Gb3) in endothelial cells and leads to life-threatening complications such as left ventricular hypertrophy (LVH), renal failure, and stroke. Enzyme replacement therapy (ERT) results in Gb3 clearance; however, because of a short half-life in the body and the high immunogenicity of FD patients, ERT has a limited therapeutic effect, particularly in patients with late-onset disease or progressive complications. Because vascular endothelial cells (VECs) derived from FD-induced pluripotent stem cells display increased thrombospondin-1 (TSP1) expression and enhanced SMAD2 signaling, we screened for chemical compounds that could downregulate TSP1 and SMAD2 signaling. Fasudil reduced the levels of p-SMAD2 and TSP1 in FD-VECs and increased the expression of angiogenic factors. Furthermore, fasudil downregulated the endothelial-to-mesenchymal transition (EndMT) and mitochondrial function of FD-VECs. Oral administration of fasudil to FD mice alleviated several FD phenotypes, including LVH, renal fibrosis, anhidrosis, and heat insensitivity. Our findings demonstrate that fasudil is a novel candidate for FD therapy. Fabry disease (FD), a lysosomal storage disorder, is caused by defective α-galactosidase (GLA) activity, which results in the accumulation of globotriaosylceramide (Gb3) in endothelial cells and leads to life-threatening complications such as left ventricular hypertrophy (LVH), renal failure, and stroke. Enzyme replacement therapy (ERT) results in Gb3 clearance; however, because of a short half-life in the body and the high immunogenicity of FD patients, ERT has a limited therapeutic effect, particularly in patients with late-onset disease or progressive complications. Because vascular endothelial cells (VECs) derived from FD-induced pluripotent stem cells display increased thrombospondin-1 (TSP1) expression and enhanced SMAD2 signaling, we screened for chemical compounds that could downregulate TSP1 and SMAD2 signaling. Fasudil reduced the levels of p-SMAD2 and TSP1 in FD-VECs and increased the expression of angiogenic factors. Furthermore, fasudil downregulated the endothelial-to-mesenchymal transition (EndMT) and mitochondrial function of FD-VECs. Oral administration of fasudil to FD mice alleviated several FD phenotypes, including LVH, renal fibrosis, anhidrosis, and heat insensitivity. Our findings demonstrate that fasudil is a novel candidate for FD therapy.
Study of the inflammatory activating process in the early stage of Fusobacterium nucleatum infected PDLSCs
Authors: Yushang Wang, Lihua Wang, Tianyong Sun, Song Shen, Zixuan Li, Xiaomei Ma, Xiufeng Gu, Xiumei Zhang, Ai Peng, Xin Xu, Qiang Feng
Journal: International Journal of Oral Science (2023)

Abstract Fusobacterium nucleatum ( F. nucleatum ) is an early pathogenic colonizer in periodontitis, but the host response to infection with this pathogen remains unclear. In this study, we built an F. nucleatum infectious model with human periodontal ligament stem cells (PDLSCs) and showed that F. nucleatum could inhibit proliferation, and facilitate apoptosis, ferroptosis, and inflammatory cytokine production in a dose-dependent manner. The F. nucleatum adhesin FadA acted as a proinflammatory virulence factor and increased the expression of interleukin(IL)-1β, IL-6 and IL-8. Further study showed that FadA could bind with PEBP1 to activate the Raf1-MAPK and IKK-NF-κB signaling pathways. Time-course RNA-sequencing analyses showed the cascade of gene activation process in PDLSCs with increasing durations of F. nucleatum infection. NFκB1 and NFκB2 upregulated after 3 h of F. nucleatum -infection, and the inflammatory-related genes in the NF-κB signaling pathway were serially elevated with time. Using computational drug repositioning analysis, we predicted and validated that two potential drugs (piperlongumine and fisetin) could attenuate the negative effects of F. nucleatum -infection. Collectively, this study unveils the potential pathogenic mechanisms of F. nucleatum and the host inflammatory response at the early stage of F. nucleatum infection.
Neural stem/progenitor cell‐derived extracellular vesicles: A novel therapy for neurological diseases and beyond
Authors: Xiangyu Li, Yingbo Zhu, Yi Wang, Xiaohuan Xia, Jialin C. Zheng
Journal: MedComm (2023)

As bilayer lipid membrane vesicles secreted by neural stem/progenitor cells (NSCs), NSC-derived extracellular vesicles (NSC-EVs) have attracted growing attention for their promising potential to serve as novel therapeutic agents in treatment of neurological diseases due to their unique physicochemical characteristics and biological functions. NSC-EVs exhibit advantages such as stable physical and chemical properties, low immunogenicity, and high penetration capacity to cross blood-brain barrier to avoid predicaments of the clinical applications of NSCs that include autoimmune responses, ethical/religious concerns, and the problematic logistics of acquiring fetal tissues. More importantly, NSC-EVs inherit excellent neuroprotective and neuroregenerative potential and immunomodulatory capabilities from parent cells, and display outstanding therapeutic effects on mitigating behavioral alterations and pathological phenotypes of patients or animals with neurological diseases. In this review, we first comprehensively summarize the progress in functional research and application of NSC-EVs in different neurological diseases, including neurodegenerative diseases, acute neurological diseases, dementia/cognitive dysfunction, and peripheral diseases. Next, we provide our thoughts on current limitations/concerns as well as tremendous potential of NSC-EVs in clinical applications. Last, we discuss future directions of further investigations on NSC-EVs and their probable applications in both basic and clinical research.
Championing inclusive terminology in ecology and evolution
Authors: Susan J. Cheng, Kaitlyn M. Gaynor, Alex C. Moore, Kathy Darragh, Cesar O. Estien, J.W. Hammond, Christopher Lawrence, Kirby L. Mills, Marcella D. Baiz, Danielle Ignace, Lily Khadempour, Matthew A. McCary, Mallory M. Rice, Shersingh Joseph Tumber-Dávila, Justine A. Smith
Journal: Trends in Ecology & Evolution (2023)
Liquid Biopsies for Cancer Genotyping: Coming of Age?
Authors: Anders Jacobsen Skanderup, Su Fen Ang, Daniel S.W. Tan
Journal: Clinical Cancer Research (2023)

Summary Precision oncology is predicated on optimal molecular profiling that is “fit for purpose” to identify therapeutic vulnerabilities. Liquid biopsies may compensate for inadequate genotyping, but remain less sensitive and specific compared with tissue biopsies. The liquid biopsy toolbox is poised to expand through novel assays and insights from longitudinal profiling. See related article by Sugimoto et al., p. 1506
Core competencies in applied infectious disease epidemiology: a framework for countries in Europe
Authors: Amelie Plymoth, Mary B Codd, Julia Barry, Adrian Boncan, Arnold Bosman, Karl F Conyard, Katarzyna Czabanowska, Nadav Davidovitch, Rodrigo Filipe, Lorena Gonzalez, Lore Leighton, John Middleton, Michael Ndirangu, Robert Otok, John Reid, Ralf Reintjes, Darren Shickle, Shiraz Syed, Patrick Wall, Jeanine Pommier
Journal: Eurosurveillance (2023)

In 2009, the European Centre for Disease Prevention and Control (ECDC) developed a competency framework to support European Union countries and the European Commission in ensuring a competent public health workforce for Europe. The coronavirus disease (COVID-19) pandemic emphasised the importance of harmonised public health strategies and competencies across international boundaries, specifically for infectious diseases. This perspective presents the process to update the competency framework for applied infectious disease epidemiology, highlighting ECDC’s efforts to support countries with using the framework. ECDC commissioned the Association of Schools of Public Health in the European Region (ASPHER) to update the framework through publication and dissemination of a technical report and a self-assessment tool linked to training resources. A mixed methods approach to gather input from experts in relevant specialities included qualitative interviews with 42 experts, workshops with ECDC Technical Advisory Group and an online survey of 212 public health professionals across Europe and beyond. Modifications resulted in 157 core competencies in 23 domains, each mapping to one of six subject areas of importance in applied infectious disease epidemiology. The framework serves as a basis to update the curriculum of the ECDC Fellowship programme with two alternative paths: intervention epidemiology or public health microbiology.
<i>QuickStats:</i> Percentage* of Adults Aged ≥45 Years Who Use a Hearing Aid,† by Sex and Age Group — National Health Interview Survey, United States, 2021§
Authors: Julie Weeks, Cynthia Reuben
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

§* With 95% CIs indicated by error bars.† Based on a positive response to the question, "Do you use a hearing aid?" § Estimates are based on household interviews of a sample of the civilian, noninstitutionalized U.S. population.In 2021, among adults aged ≥45 years, men were more likely to use a hearing aid than were women (9.2% versus 5.5%).This pattern was found in all age groups: 3.0% of men versus 1.4% of women among those aged 45-64 years, 12.3% versus 5.7% among those aged 65-74 years, 26.7% versus 13.7% among those aged 75-84 years, and 39.5% versus 31.5% among those aged ≥85 years.Among both men and women, the percentage who use a hearing aid increased with age.
Cancer in Transgender and Gender-Diverse Persons
Authors: Alberto Giovanni Leone, Dario Trapani, Matthew B. Schabath, Joshua D. Safer, N. F. N. Scout, Matteo Lambertini, Rossana Berardi, Silvia Marsoni, Francesco Perrone, Saverio Cinieri, Rosalba Miceli, Federica Morano, Filippo Pietrantonio
Journal: JAMA Oncology (2023)

Transgender and gender-diverse individuals face unique challenges, including barriers to health care access and inequities in treatment, that may influence cancer risk and outcomes.In this narrative review, a scoping review was conducted focusing on primary and secondary prevention and epidemiology of cancer, barriers to health care services, and health care practitioners' knowledge about specific issues pertaining to transgender and gender-diverse individuals. PubMed, the Cochrane Library, and Embase, were reviewed for citations from their inception to December 31, 2021. This review revealed that transgender and gender-diverse people had a high prevalence of tobacco consumption and alcohol use and high rates of infection with human papillomavirus (HPV) and HIV. Transgender and gender-diverse individuals were less likely to adhere to cancer screening programs and had a higher incidence of HIV- and HPV-associated cancers. Social and economic determinants seemed to drive these disparities in risk factors and outcomes. A lack of knowledge about gender minorities' health needs among health care practitioners was evidenced, and it represented a major hurdle to cancer prevention, care, and survivorship for transgender and gender-diverse individuals. Discrimination, discomfort caused by gender-labeled oncological services, stigma, and lack of cultural sensitivity of health care practitioners were other barriers met by transgender and gender-diverse persons in the oncology setting.The findings suggest that transgender and gender-diverse peoples' needs in the cancer care continuum are not optimally addressed. Effective solutions are needed to offer the best care to every patient in a person-centric and gender diversity-sensitive environment.
Reclassification of the Etiology of Infant Mortality With Whole-Genome Sequencing
Authors: Mallory J. Owen, Meredith S. Wright, Sergey Batalov, Yonghyun Kwon, Yan Ding, Kevin K. Chau, Shimul Chowdhury, Nathaly M. Sweeney, Elizabeth Kiernan, Andrew Richardson, Emily Batton, Rebecca J. Baer, Gretchen Bandoli, Joseph G. Gleeson, Matthew Bainbridge, Christina D. Chambers, Stephen F. Kingsmore
Journal: JAMA Network Open (2023)

Understanding the causes of infant mortality shapes public health, surveillance, and research investments. However, the association of single-locus (mendelian) genetic diseases with infant mortality is poorly understood.
Advisory Committee on Immunization Practices Recommended Immunization Schedule for Adults Aged 19 Years or Older — United States, 2023
Authors: Neil Murthy, A. Patricia Wodi, Veronica McNally, Sybil Cineas, Kevin Ault
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

At its October 2022 meeting, the Advisory Committee on Immunization Practices* (ACIP) approved the Recommended Adult Immunization Schedule for Ages 19 Years or Older, United States, 2023. The 2023 adult immunization schedule summarizes ACIP recommendations, including several changes to the cover page, tables, notes, and appendix from the 2022 immunization schedule.† This schedule can be found on the CDC immunization schedule website (https://www.cdc.gov/vaccines/schedules). Health care providers are advised to use the cover page, tables, notes, and appendix together to determine recommended vaccinations for patient populations. This adult immunization schedule is recommended by ACIP (https://www.cdc.gov/vaccines/acip) and approved by CDC (https://www.cdc.gov), the American College of Physicians (https://www.acponline.org), the American Academy of Family Physicians (https://www.aafp.org), the American College of Obstetricians and Gynecologists (https://www.acog.org), the American College of Nurse-Midwives (https://www.midwife.org), the American Academy of Physician Associates (https://www.aapa.org), the American Pharmacists Association (https://www.pharmacist.com), and the Society for Healthcare Epidemiology of America (https://shea-online.org).
Synergistic Association of Hepatitis B Surface Antigen and Plasma Epstein-Barr Virus DNA Load on Distant Metastasis in Patients With Nasopharyngeal Carcinoma
Authors: Haojiang Li, Di Cao, Shuqi Li, Binghong Chen, Yun Zhang, Yuliang Zhu, Chao Luo, Weiqun Lin, Wenjie Huang, Guangying Ruan, Rong Zhang, Jiang Li, Lizhi Liu
Journal: JAMA Network Open (2023)

Importance Hepatitis B surface antigen (HBsAg) reportedly increases the risk of distant metastasis among patients with nasopharyngeal carcinoma (NPC). However, the associated potential interaction and changes in hazard ratios (HRs) between HBsAg and different plasma Epstein-Barr (EBV) DNA levels are unknown. Moreover, the potential HBsAg-positive–associated NPC metastatic mechanism remains unclear. Objective To investigate the prognostic value and biological associations of HBsAg and plasma EBV DNA levels on distant metastasis in patients with NPC. Design, Setting, and Participants Retrospective cohort study performed at Sun Yat-sen University Cancer Center between January 2010 and January 2013. A total of 792 patients with nonmetastatic NPC were enrolled. The median (range) follow-up time was 62.1 (1.4-83.4) months. Of these patients, 17.8% presented with HBsAg positivity. Cytological experiments were performed to evaluate the role of HBsAg in the invasion and migration of EBV-positive NPC cells. Data analysis was performed from July 2020 to April 2021. Main Outcomes and Measures The primary end point was distant metastasis–free survival. Association rules were used to identify new rules related to distant metastasis. Interaction plots, univariate and multivariate Cox regression analyses, stratification analysis, and quantification using HRs were conducted. Additionally, cell migration and invasion assays, as well as Western blotting, were performed in the cytological validation. Results Among the 792 patients, 576 (72.7%) were male, with a median (IQR) age of 45 (38-53) years. The HBsAg-positive group exhibited a significant interaction and increased risk of distant metastasis when plasma EBV DNA cutoff levels were 1.5 × 1000 copies/mL or greater. The HR was 9.16 (95% CI, 2.46-34.14) when the plasma EBV DNA load reached 6 × 1000 copies/mL, which was higher than that in patients with stage IV disease (HR, 2.01; 95% CI, 1.13-3.56; P = .02). In cytological experiments, HBsAg promoted epithelial-mesenchymal transition by upregulating vimentin and fibronectin in EBV-positive NPC cells in vitro, thereby promoting invasion and migration of EBV-positive NPC cells. Conclusions and Relevance In this cohort study, the observed synergistic association between HBsAg and plasma EBV DNA load represented a novel potential mechanism underlying the increased risk of distant metastasis in patients with NPC. Hence, attention should be paid to patients with NPC with HBsAg positivity, especially when the plasma EBV DNA level is 6 × 1000 copies/mL or greater. Consideration of this synergistic association will contribute to more accurate individualized management.
Association of Recent SARS-CoV-2 Infection With New-Onset Alcohol Use Disorder, January 2020 Through January 2022
Authors: Veronica R. Olaker, Ellen K. Kendall, Christina X. Wang, Theodore V. Parran, Pauline Terebuh, David C. Kaelber, Rong Xu, Pamela B. Davis
Journal: JAMA Network Open (2023)

Importance The COVID-19 pandemic affects many diseases, including alcohol use disorders (AUDs). As the pandemic evolves, understanding the association of a new diagnosis of AUD with COVID-19 over time is required to mitigate negative consequences. Objective To examine the association of COVID-19 infection with new diagnosis of AUD over time from January 2020 through January 2022. Design, Setting, and Participants In this retrospective cohort study of electronic health records of US patients 12 years of age or older, new diagnoses of AUD were compared between patients with COVID-19 and patients with other respiratory infections who had never had COVID-19 by 3-month intervals from January 20, 2020, through January 27, 2022. Exposures SARS-CoV-2 infection or non–SARS-CoV-2 respiratory infection. Main Outcomes and Measures New diagnoses of AUD were compared in COVID-19 and propensity score–matched control cohorts by hazard ratios (HRs) and 95% CIs from either 14 days to 3 months or 3 to 6 months after the index event. Results This study comprised 1 201 082 patients with COVID-19 (56.9% female patients; 65.7% White; mean [SD] age at index, 46.2 [18.9] years) and 1 620 100 patients with other respiratory infections who had never had COVID-19 (60.4% female patients; 71.1% White; mean [SD] age at index, 44.5 [20.6] years). There was a significantly increased risk of a new diagnosis of AUD in the 3 months after COVID-19 was contracted during the first 3 months of the pandemic (block 1) compared with control cohorts (HR, 2.53 [95% CI, 1.82-3.51]), but the risk decreased to nonsignificance in the next 3 time blocks (April 2020 to January 2021). The risk for AUD diagnosis increased after infection in January to April 2021 (HR, 1.30 [95% CI, 1.08-1.56]) and April to July 2021 (HR, 1.80 [95% CI, 1.47-2.21]). The result became nonsignificant again in blocks 7 and 8 (COVID-19 diagnosis between July 2021 and January 2022). A similar temporal pattern was seen for new diagnosis of AUD 3 to 6 months after infection with COVID-19 vs control index events. Conclusions and Relevance Elevated risk for AUD after COVID-19 infection compared with non–COVID-19 respiratory infections during some time frames may suggest an association of SARS-CoV-2 infection with the pandemic-associated increase in AUD. However, the lack of excess hazard in most time blocks makes it likely that the circumstances surrounding the pandemic and the fear and anxiety they created also were important factors associated with new diagnoses of AUD.
Effect of Silver Diamine Fluoride on Caries Arrest and Prevention
Authors: Ryan Richard Ruff, Tamarinda Barry-Godín, Richard Niederman
Journal: JAMA Network Open (2023)

Importance Dental caries is the most common global childhood disease. To control caries, the Centers for Disease Control and Prevention recommends school-based caries prevention, and the World Health Organization lists glass ionomer cement and silver diamine fluoride as essential medicines for oral disease. Objective To determine the noninferiority of silver diamine fluoride with fluoride varnish vs traditional glass ionomer sealants with fluoride varnish after 2 years when provided to children via a school-based health care program. Design, Setting, and Participants The CariedAway study is an ongoing single-blind, cluster randomized, noninferiority trial conducted between February 1, 2019, and June 1, 2023, among 2998 children in 47 New York City primary schools. Children aged 5 to 13 years of any race and ethnicity were recruited from block-randomized schools. Inclusion criteria for schools were a student population of at least 50% Hispanic or Latino or Latina ethnicity and/or Black race and at least 80% of students receiving free or reduced-cost lunch. Statistical analysis is reported through March 2022. Interventions Children received a single application of silver diamine fluoride with fluoride varnish or an active comparator of glass ionomer sealants and atraumatic restorations with fluoride varnish. Main Outcomes and Measures Primary outcomes were caries arrest and incidence after a 2-year follow-up, assessed using mixed-effects multilevel models and clustered 2-sample proportion tests. The noninferiority margin was 10%. Intention-to-treat analysis was performed using multiple imputation. Results A total of 2998 children (1566 girls [52.2%]; mean [SD] age at baseline, 6.6 [1.2] years; 1397 Hispanic or Latino or Latina children [46.6%]; 874 [29.2%] with untreated dental caries) were recruited and treated from September 16, 2019, to March 12, 2020. Follow-up observations were completed for 1398 children from June 7, 2021, to March 2, 2022. The mean (SE) proportion of children with arrested caries was 0.56 (0.04) after experimental treatment and 0.46 (0.04) after control treatment (difference, −0.11; 95% CI, −0.22 to 0.01). The mean (SE) proportion of patients without new caries was 0.81 (0.02) after experimental treatment and 0.82 (0.02) after control treatment (difference, 0.01; 95% CI, −0.04 to 0.06). Analysis of imputed data for the full sample did not deviate from per-protocol analyses. There were no adverse events. Conclusions and Relevance In this randomized clinical trial, silver diamine fluoride with fluoride varnish was noninferior to sealants and atraumatic restorations with fluoride varnish for caries arrest and prevention. Results may support the use of silver diamine fluoride as an arresting and preventive agent in school-based oral health programs. Trial Registration ClinicalTrials.gov Identifier: NCT03442309